C2H2 Zinc Finger Proteins (Over 700 in Number and 3% of Human Proteome) Have Evolved from Inhibitors of Endogenous Retro-Elements (EREs) to Transcription Factors

University of Toronto scientists have discovered how viral remnants helped shape control of our genes. If genes were lights on a string of DNA, the genome would appear as an endless flicker, as thousands of genes come on and off at any given time. Dr. Tim Hughes, a Professor at the University of Toronto's Donnelly Centre, has been focused on unraveling the rules behind this tightly orchestrated light-show, because, when it fails, disease can occur. Genes are switched on or off by proteins called transcription factors. These proteins bind to precise sites on the DNA that serve as guideposts, telling transcription factors that their target genes are nearby. In an article published online on February 18, 2015 in Nature Biotechnology, Dr. Hughes and his team describe the first systematic study of the largest group of human transcription factors, called C2H2-Zinc Finger (C2H2-ZF) transcription factors (image shows the general structure of these transcription factors). The Nature Biotechnology article is titled “C2H2 Zinc Finger Proteins Greatly Expand the Human Regulatory Lexicon.” Despite their important roles in development and disease, these proteins have remained largely uninvestigated because they posed a formidable challenge to researchers. C2H2-ZF transcription factors constitute a group of over 700 proteins, approximately 3 per cent of all human genes. To make matters more complicated, most human C2H2-ZF transcription factors are very different from C2H2-ZF transcription factors in other organisms, such as those in mice, for example. This means that scientists can not apply insights gained from animal studies to human C2H2-ZFs. In their new work, Dr.
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